"Transmission electron microscopy (EM) is used as an adjunct procedure in the diagnosis of a wide range of neoplastic and non neoplastic diseases and can be extremely useful in well chosen diagnostic dilemmas.The main objectives of the diagnostic EM service are: (1) to provide EM diagnosis in patient specimens (2) to contribute to the understanding of the pathogenesis of diseases studied in various NIH protocols and (3) to assist investigators in research protocols with specific EM-related questions. The last year's accomplishments are summarized below. (1) A total of 118 patient tissues were processed and diagnosed by EM. (2) An additional 172 research specimens were processed and evaluated for research protocols (3) EM was instrumental in identifying the mitochondrial damage caused by the drug fialuridine that was used in NIH trials (4) EM was instrumental in defining that the achlorydric gastritis that was detected in patients with mycolipidosis type IV by NIH cllnicians was not due to lack of parietal cells, but rather to dysfunctional parietal cells because of storage material in giant lysosomes. (5) EM was important in showing that patients with the dysmorphic Smith-Lemli-Opitz syndrome, in addition to their primary defect in cholesterol biosynthesis may have a secondary defect in the degradation of intracellular low denisity lipoproteins (LDL), resulting in abnormal accumulation of unesterified sterols and lysosomal inclusions similar to those seen in Niemann Pick disease. (6) EM played a role in the morphologic characterization of reticulum cell neoplasms in lymph nodes."